PMID- 36940581 OWN - NLM STAT- MEDLINE DCOM- 20230428 LR - 20240328 IS - 1873-6750 (Electronic) IS - 0160-4120 (Linking) VI - 174 DP - 2023 Apr TI - Thirdhand tobacco smoke exposure increases the genetic background-dependent risk of pan-tumor development in Collaborative Cross mice. PG - 107876 LID - S0160-4120(23)00149-6 [pii] LID - 10.1016/j.envint.2023.107876 [doi] AB - Increasing evidence has shown that thirdhand smoke (THS) exposure is likely to induce adverse health effects. An important knowledge gap remains in our understanding of THS exposure related to cancer risk in the human population. Population-based animal models are useful and powerful in investigating the interplay between host genetics and THS exposure on cancer risk. Here, we used the Collaborative Cross (CC) mouse population-based model system, which recapitulates the genetic and phenotypic diversity observed in the human population, to assess cancer risk after a short period of exposure, between 4 and 9 weeks of age. Eight CC strains (CC001, CC019, CC026, CC036, CC037, CC041, CC042 and CC051) were included in our study. We quantified pan-tumor incidence, tumor burden per mouse, organ tumor spectrum and tumor-free survival until 18 months of age. At the population level, we observed a significantly increased pan-tumor incidence and tumor burden per mouse in THS-treated mice as compared to the control (p = 3.04E-06). Lung and liver tissues exhibited the largest risk of undergoing tumorigenesis after THS exposure. Tumor-free survival was significantly reduced in THS-treated mice compared to control (p = 0.044). At the individual strain level, we observed a large variation in tumor incidence across the 8 CC strains. CC036 and CC041 exhibited a significant increase in pan-tumor incidence (p = 0.0084 and p = 0.000066, respectively) after THS exposure compared to control. We conclude that early-life THS exposure increases tumor development in CC mice and that host genetic background plays an important role in individual susceptibility to THS-induced tumorigenesis. Genetic background is an important factor that should be taken into account when determining human cancer risk of THS exposure. CI - Copyright (c) 2023. Published by Elsevier Ltd. FAU - Yang, Hui AU - Yang H AD - Department of Radiation and Medical Oncology, Hubei Key Laboratory of Tumor Biological Behaviors, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, China. FAU - Wang, Xinzhi AU - Wang X AD - College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210046, China. FAU - Wang, Pin AU - Wang P AD - Department of Gastroenterology, Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China. FAU - He, Li AU - He L AD - Department of Hematology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, China. FAU - Schick, Suzyann F AU - Schick SF AD - Department of Medicine, Division of Occupational and Environmental Medicine, University of California, San Francisco, CA 94143, USA. FAU - Jacob, Peyton 3rd AU - Jacob P 3rd AD - Department of Medicine, Division of Cardiology, Clinical Pharmacology Program, University of California, San Francisco, CA 94143, USA. FAU - Benowitz, Neal AU - Benowitz N AD - Department of Medicine, Division of Cardiology, Clinical Pharmacology Program, University of California, San Francisco, CA 94143, USA. FAU - Gundel, Lara A AU - Gundel LA AD - Indoor Environment Group, Energy Technologies Area, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA. FAU - Zhu, Chi AU - Zhu C AD - Hanszen College, Rice University, Houston, TX 77005, USA. FAU - Xia, Yankai AU - Xia Y AD - State Key Laboratory of Reproductive Medicine, Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing 211166, China. FAU - Inman, Jamie L AU - Inman JL AD - Biological Systems and Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA. FAU - Chang, Hang AU - Chang H AD - Biological Systems and Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA. FAU - Snijders, Antoine M AU - Snijders AM AD - Biological Systems and Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA. Electronic address: amsnijders@lbl.gov. FAU - Mao, Jian-Hua AU - Mao JH AD - Biological Systems and Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA. Electronic address: jhmao@lbl.gov. FAU - Hang, Bo AU - Hang B AD - Biological Systems and Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA. Electronic address: Bo_Hang@lbl.gov. LA - eng GR - P30 DA012393/DA/NIDA NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20230313 PL - Netherlands TA - Environ Int JT - Environment international JID - 7807270 RN - 0 (Tobacco Smoke Pollution) SB - IM MH - Humans MH - Animals MH - Mice MH - *Tobacco Smoke Pollution/adverse effects MH - Collaborative Cross Mice MH - Risk Factors MH - *Neoplasms/etiology/genetics MH - Carcinogenesis/genetics/chemically induced MH - Cell Transformation, Neoplastic OTO - NOTNLM OT - Collaborative Cross (CC) mice OT - Genetic susceptibility OT - Pan-tumor incidence OT - Thirdhand smoke (THS) OT - Tumor burden OT - Tumor-free survival OT - Tumorigenesis COIS- Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2023/03/21 06:00 MHDA- 2023/04/28 06:42 CRDT- 2023/03/20 19:03 PHST- 2022/12/24 00:00 [received] PHST- 2023/02/15 00:00 [revised] PHST- 2023/03/09 00:00 [accepted] PHST- 2023/04/28 06:42 [medline] PHST- 2023/03/21 06:00 [pubmed] PHST- 2023/03/20 19:03 [entrez] AID - S0160-4120(23)00149-6 [pii] AID - 10.1016/j.envint.2023.107876 [doi] PST - ppublish SO - Environ Int. 2023 Apr;174:107876. doi: 10.1016/j.envint.2023.107876. Epub 2023 Mar 13.